title: Hepatic loss of survivin impairs postnatal liver development and promotes expansion of hepatic progenitor cells in mice.
abstract: Hepatocytes possess a remarkable capacity to regenerate and reconstitute the parenchyma after liver damage. However, in the case of chronic injury, their proliferative potential is impaired and hepatic progenitor cells (HPCs) are activated, resulting in a ductular reaction known as oval cell response. Proapoptotic and survival signals maintain a precise balance to spare hepatocytes and progenitors from hyperplasia and cell death during regeneration. Survivin, a member of the family of inhibitor of apoptosis proteins (IAPs), plays key roles in the proliferation and apoptosis of various cell types. Here, we characterized the in vivo function of Survivin in regulating postnatal liver development and homeostasis using mice carrying conditional Survivin alleles. Hepatic perinatal loss of Survivin causes impaired mitosis, increased genome ploidy, and enlarged cell size in postnatal livers, which eventually leads to hepatocyte apoptosis and triggers tissue damage and inflammation. Subsequently, HPCs that retain genomic Survivin alleles are activated, which finally differentiate into hepatocytes and reconstitute the whole liver. By contrast, inducible ablation of Survivin in adult hepatocytes does not affect HPC activation and liver homeostasis during a long-life period.
  
  
  CONCLUSIONS
  Perinatal Survivin deletion impairs hepatic mitosis in postnatal liver development, which induces HPC activation and reconstitution in the liver, therefore providing a novel HPC induction model.
authors.affiliation: Graduate University of Chinese Academy of Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China; State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Jin
authors.initials: J
authors.lastname: Cen
authors.forename: Xiaotao
authors.initials: X
authors.lastname: Chen
authors.forename: Edward M
authors.initials: EM
authors.lastname: Conway
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ji
authors.forename: Lijian
authors.initials: L
authors.lastname: Hui
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002454:Cell Differentiation; D022781:Hepatocytes / Q000166:cytology*; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D008099:Liver / Q000254:growth & development* / Q000473:pathology; D008115:Liver Regeneration / Q000502:physiology; D051379:Mice; D012097:Repressor Proteins / Q000235:genetics*; D013234:Stem Cells / Q000166:cytology*; D000077022:Survivin
chemical_list: C117749:Birc5 protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D012097:Repressor Proteins; D000077022:Survivin